You need to get calories from somewhere, should it be from carbohydrate or fat?

Tuesday, January 17, 2012

Used brain for sale: One careful owner, only slightly broken

Let's start with the old Stranglers track, "No More Heros", take an ice pick to a rat's brain and make its ears burn. OK, chew up its ventromedial hypothalamus with an electrolysis needle. This French paper is a pdf.

Here's the interesting table from the results:

At week one, when weight gain has started but not gone very far, fasting insulin was unchanged but blood glucose was LOWER than that of control rats. These rats, with their brain injury, have increased whole body insulin sensitivity. Mostly prominently in their adipocytes. The paper mentions in the discussion that these rats also hyper secrete insulin in response to secretagogues. Now, as we all know, insulin is both anorexic and unimportant to weight control. But if you just imagined, as I do, for a second that insulin does have something to do with weight gain, what would you expect to happen if you dropped hyper-secreted insulin on to exquisitely insulin sensitive adipocytes? Their job is to store fat under the influence of insulin so...

They would store fat. They would hang on to it. As Taubes might comment, the rats then over-eat because they are losing calories in to their adipocytes. They over eat because they are becoming fat. How do you check this? Well, let's pair feed ice-picked rats with control rats. Limit their calories. Make them go to uncheatable Weight Watchers in a prison cage. From the discussion:

"However pair-feeding rats with controls does not prevent excessive lipogenesis, fat accumulation and hyperinsulinemia [48, 49], suggesting that the disturbances of metabolism and not hyperphagia are the primary factors leading to obesity."

You injure the brain, alter the adipocytes and they store fat. Hyperphagia is an epiphenomenon of calories lost to adipocytes. They store fat even WITHOUT hyperphagia. This was quite obvious in 1992.

Enough frivolity. Let's get slightly more up to date with some Spanish MSG rats.

You have to be a bit careful with MSG injured rats. MSG is a potent neurotoxin and kills or injures almost any cell sporting glutamate receptors. This includes large numbers of nerve cells in the VMH, the target of the electrical ice-pick. However it also blunts growth hormone production, shuts down thermogenesis from brown adipose tissue and, very interestingly, adipocytes themselves probably use glutamic acid for cross talk purposes, so it's hard to know exactly what we do to MSG treated rats in addition to busting their VMH. You have to wonder whether the adipocytes themselves are injured by MSG.

Anyway, at a month of age, MSG injured rats have highly insulin sensitive adipocytes. Before the rats have become visibly obese their fat cells are already somewhat swollen and ready for the off in to full blown blobby-ness, come puberty. So again, you bust the VMH, increase adipocyte insulin sensitivity, adipocytes suck in fat and your rat simply has to eat to maintain access to enough energy to stay alive and cart the inaccessible fat around its cage. It probably doesn't dream of going to the gym.

If adipocytes are hypersensitive to insulin, what would you expect fasting FFAs, glucose and insulin look like before obesity developed?

Eyeball the HOMA score! These rats are a picture of glucoregulatory health! Unfortunately you need an energy supply from somewhere and some extra FFAs might just sort that out. You really need to develop some adipocyte distension induced insulin resistance by becoming obese to get the FFAs up to an appropriate level for a fasting rat. That's just what they do...

Cool, huh? Unfortunately we don't have the FFA level in the paper but, looking at the adipocyte size, they will be leaking FFAs in defiance of their double-the-control-rat level of insulin.

Now, are these adult, distended adipocytes insulin sensitive or resistant?

Well, they do bugger all to increase glucose uptake with increasing insulin exposure. So yes, they are insulin resistant. But look at this:

What glucose they do take up is diverted to fat. Might we say they are behaving like muscle cells which lack metabolic flexibility? Mitochondrial injury?

So, as obesity becomes established we end up in the age old situation of insulin resistant distended adipocytes leading to more FFA leakage than appropriate for a given level of insulin and so hyperinsulinaemia develops to try to keep blood glucose normal in the face of chronically elevated FFAs. This is absolutely not the case in the very early days, but rapidly becomes so with time.

This is all quite straight forwards and nothing you wouldn't expect if you accept the importance of insulin in obesity, adipocyte hypertrophy induced insulin resistance and the fact that adipocytes have a nerve supply which regulates their insulin sensitivity. In fact there are interesting papers on the role of adrenal hormones and the vagus as well as the sympathetic nervous system in MSG injury induced obesity. The end result is always increased insulin sensitivity of adipocytes until they become over-distended.

You can, of course, do exactly the same with gold thioglucose. Getting bored with all this? I'd basically come to the conclusion that VMH injuries give the impression of causing hyperphagia when what they actually do is increase lipid loss in to adipocytes, under the influence of insulin.

Okaaaay.

Let's look at a Long-Evans rat. If you feed it on D12492, which has been described as a high fat diet, for just three days, its brain breaks.

What if it is the fat that breaks the brain?

Well, my brain is then going to be completely f*cked.

I really do think that it might just be the fat that does it. How do I know? God told me. Okay, okay, only kidding. About god.

No, James emailed me a link to the latest Schwartz offering. I suspect that Dr Schwartz does not like Gary Taubes. We can also skip to the blog of the 4th author, who certainly does not like Gary Taubes, load up on ondansetron and have a browse. The blog says:

"Based on previous studies, the dietary fat itself is probably an important component that makes D12492 fattening in rodents"

The man is correct.

If you have quite recovered from that, let's look at the simpler aspects of the study. We can come back to the superb electron micrographs of dying mitochondria some other time. BTW, they are very, very cool pictures. I've been looking for similar photomicrographs all over the place. Who would have thought I would have found them here? Anyhoo:

Start some ratties on D12492 and they will immediately double their calorie intake, on day 1. After living your whole short life eating CIAB I can understand this. D12492 tastes so good you just can't help yourself and it must be quite easy to eat enough of it to break your brain. It must be very rewarding. Luckily your brain recovers a bit and soon, by day seven, you're not eating any more calories of D12492 than a rat on CIAB and that's how it stays for the full 28 day period. We can tell this from Graph G. Here the average 28d food consumption on D12492 is only just above the 14d average consumed as CIAB. This excess is mostly accounted for by the first seven days of hyperphagia.

The bit of the brain which breaks "in association" with the massive 60% of calories from fat is the good old VMH. If we go back to the ice-pick rats, the MSG rats and the gold thioglucose rats we might just develop the suspicion that breaking the brain of a Long-Evans rat might affect the insulin sensitivity of its adipocytes.

If it does, fat from the diet will simply pour in to the adipose tissue and the unfortunate rattie will then have to eat extra to supply some energy to run its metabolism on in addition to that used for filling its adipocytes. Initially twice the amount it ate on CIAB. As the adipocytes fill they will become intrinsically less sensitive to insulin and fat accumulation, with its necessary compensatory hyperphagia, will slow. But not stop, if they behave anything like adipocytes in other VMH injured rat models.

On a high fat diet there is plenty of fat to pour in to adipocytes, no lipogenesis is needed. Adipocytes can distend quickly and it would be interesting to see if the fasting hypoinsulinaemia seen in the MSG rats (fed on high carbohydrate CIAB) occurs in D12492 injured rats. Probably it would still occur but be very transient, but obviously no one in the Schwartz lab would be interested in insulin.

Of course, one has to wonder which component of the D12492 might injure a rat's VMH. We are all familiar with the conversation (scroll up to get to the text) between Chris Masterjohn and the good doctor, where the omega 6 PUFA content of D12492 was noted to be 32% of fat and the omega 6:3 ratio was 14 or 16:1. All fascinating background. But my favourite obesity researcher correctly thinks it is the fat, not the type of fat, which breaks the VMH.

You can do exactly the same with butter oil (plus a smidge of soybean oil), which I'm guessing is a bit like ghee. Which I rather like. This is what butter oil at 20g/100g of food does to a Long-Evans rat in this study:

In particular look at what happened to the group HF. They switched from non purified (NP) diet on day 1 on the graph, spiked their intake to about 50% extra calories by day 5ish and were almost back down to the NP group's caloric intake by day 10. Exactly the same pattern as the D12492 also produces in Long-Evans rats.

It is impossible to emphasise how important both studies are to you if you are a Long-Evans rat.

Does three days of high fat eating break your brain if you are a human being? I have to admit that I appear to have singularly failed to become obese on 80% of my calories as fat over nine years. Possibly because 80% of your calories from fat becomes protective? I dunno. I can't help but recall those chaps in Aberdeen eating 66% of their calories as fat and refusing to finish off their allotted 2000kcal/d...

I have to be open to the idea that humans may not respond to high fat feeding in quite the same way as Long-Evans rats do. OK, they just don't. Their VMH doesn't acutely break. The rat is in trouble on 60% of calories as any sort of fat. Humans just say "no thank you" to the extra slice of bacon, in Aberdeen anyway. Oh, and in Lowestoft too.

In summary: Injuring your VMH in any way (even by eating butter oil if you are a Long-Evans rat) does nasty things to your adipocytes. They will store fat even if you cut calories. You will then be very hungry and, unless you do eat more, you will chew up your muscles for energy, get cold and move as little as possible. Oh, and still get fat. People will say you lie about your calorie intake.

Now, is it possible to become obese without breaking your VMH? Of course it is. Does it matter? That depends.

I think the chronic changes in both the Long-Evans rats and the C57BL/6 mice are very important and are quite likely different from the initial fat induced injury to the VMH. They appear to be more related to the chronic hyperinsulinaemia and hyperglycaemia which follow on from adipocyte insulin resistance and elevated FFAs especially in the presence of a high dietary carbohydrate intake. That will lead us to back to mitochondrial injury (which is probably where all of this comes from, did I even mention that obesity is a mitochondrial problem?), free radicals and I might even throw in gliosis. Which is interesting.

118 comments:

I have been following your blog for about 2 months now and I've been gradually approaching a HF/LC diet.

One problem that I'm worrying about though is whether after cutting out grains and limiting vegetables, is it possible that one is running a risk of micro-nutrient deficiency? Animal fat and protein do not supply ample sources of minerals like magnesium, manganese, and phosphorous.

Nuts/legumes are typically high in these nutrients but they have the problem of distorted omega 3 to 6 ratios, as well as the possibility of auto immune problems in the case of some nuts as well as many types of beans. In following the OD isn't one forgoing these micronutrients? Might this be a serious problem, seeing as these nutrients are important for many things like proper bone development and nerve transmission?

Here's an idea for floating; I'm interested in what happens in people with normal or low weight with IR. Is it reasonable to suggest that glucose and lipids are being "stored" in the blood (as it were) and this causes disease? 8 pints of skim milk vs 8 pints of sweteened and cream-saturated stuff?There is also the fat excretion in coeliac disease as another route for the unhealthy prevention of obesity?Where do the "calories" (if there is such a thing) go in hungry normal-weight IR?

It is my thinking that obesity has very little (or at least, less) to do with insulin resistance, and EVERYTHING to do with inappropriate, genetic/endocrine effects that result in abnormal adipocyte hypersensitivity to insulin signalling. This is why you can find many people, usually reproductive aged females, who have no signs of insulin resistance, but they are like 4,000 pounds. It need not require insulin resistance, total body insulin sensitivity may be still adequate, but you will be very very fattoes if your fat tissue is good about responding to insulin. (The reason this is more common in reproductive aged females is because estrogen/progesterone enhance fat cell insulin sensitivity + differentiation, and explains the observation, mentioned by Taubes in GCBC, that low income obesity prone populations, with an aggregation of genetics from hunter-gatherers, will find extremely obese women and children/men are relatively obesity resistant).

I wonder if hypothalamic damage mediates these effects by obliterating leptin-sensitive neurons. The changes in insulin and fat cell function is very much like leptin deficiency. The way these rodents behave is a lot like starvation - sequestering energy AWAY from lean tissue directing it TOWARD fat tissue.

I also suspect that hyperphagia is absolutely an effect of adipocyte growth, but it is probably also an independent effect of hypothalamic damage. Both can occur simultaneously and hyperphagia independent of that which is mediated by adipocyte growth, would further enhance survival in emaciation (which, hypothalamic damage possibly orients the physiology around, possibly by blowing up a major critical site for leptin signalling).

Of course none of this would have anything to do with garden variety obesity, where the hypothalamus is not damaged by lesioning, MSG/diet.There may be some forms of obesity which are hypothalamic damage - leptin resistant, but I am of the opinion that common obesity is nothing more than an aggregation of genetic traits selected by hunter gatherers to optimize fat storage seasonally. This is why it is found to concentrate along ethnic lines (fact, aframs/latin americans have tons of hunter gatherer genes compared to caucasians/east asians). I believe the genes work by modulating glucose tolerance, dopamine activity and other factors... and to a person with this genetic vulnerability, a high glucose diet reads like "seasonal opportunity" and whole physiology changes to promote fat storage. The problem is when the person finds themselves in an agricultural environment, and winter / lack of fat animals / lack of vegetation never comes. But that is HIGHLY speculative and hypothetical.

OH WAIT, NEVERMIND, IT'S ALL REWARD, AND PPL JUST EAT TOO MUCH AND THIS CAUSES IR WITH SECONDARY INSULIN ABNORMALITIES.

This means I eat 1 cup broccoli for breakfast, 1 cup spinach for lunch with 4 spears of asparagus, with 1 cup steamed cauliflower with 4 cups (1 quart) mixed baby lettuce for dinner. This means I eat about 8-9 cups of veggies a day, with some carbs left over for eggs and cream.

Sometimes I mix up the spinach for some brightly colored veggies. Poor me.

Gosh, do you think 9 cups of veggies a day is enough? I suspect it's more than most "vegetarians" eat.

"You can do exactly the same with butter oil (plus a smidge of soybean oil), which I'm guessing is a bit like ghee."

Is a fat including a substantial amount of linoleic acid required?

Emily Dean mentions, "Here's the evolutionary psychiatry money quote from the Wang article: 'Some ingredients in palatable food such as sugar and corn oil can result in impulsive ingestion in patterns reminiscent of those seen with drug intake in addiction.'"

Regarding the lack of food increase, I don't see how one couldn't use that same argument with food reward, where the definition is its ability to reinforce behavior. If you think that the reward value is simply lowered quickly, then why does their fat mass continues to rise along with their decreasing caloric intake? Why aren't their "setpoints," and consequently, bodyfat, getting lowered as their boredom increases?

Fortune is right. Most of the people I've known who go HF/LC eat far more vegetables than before. What is cut back is starches and grains, s well as most fruits, but there is usually a large rise in consumption of cruciferous vegetables, salad greens, green beans, spinach, etc. (Many also become fans of berries.)

I'd ignore the Masai as an example of anything--or at the minimum, read Chris Masterjohn on the topic. ("I also think we tend to take an androcentric view of the Masai. We emphasize their exclusive diet of meat, blood, and milk — and tea, which we ignore because it is made from plants — even though this exclusive diet is only eaten by males during a certain stage of their life and is never eaten by women.")

If you're losing a lot of weight on HF/LC, you should indeed be cautious about minerals--especially potassium and magnesium, which tend to be depeleted by rapid weight loss...

What it supports is the old hat, boring, unpopular among academic elites, unscientific, fat middle state american idea that insulin signalling in adipocytes leads to fat growth, which then leads to over eating and "compulsive food intake reminiscent of addiction".

If you blow up a rat's hypothalamus, their FAT CELLS change function and become hypersensitive to insulin. It is a way of inducing abnormal adipocyte hypersensitivity to insulin and fattening - this is how obesity develops.

Metabolic parameters initially improve compared to normal rats because of this (they are very effective at stealing triglycerides and glucose, and insulin is actually a bit lower). As the adipocyte expands because of this process, it becomes distended, metabolic problems/resistance to insulin will then set in, but not before BECOMING A BIG FAT STACK. The IR does not cause obesity, it is a RESULT of obesity, which is a result of insulin signalling in adipocytes.

The graph, in isolation, can promote food reward. It can also promote a theory that not getting enough love as a baby rat leads to over eating, due to the cruel handling of the scientists. Anyone can make up any random unfalsifiable untestible hypothesis to retroactively explain why an animal or human begins eating more.

When you look at the totality of the evidence (The changes in insulin signalling and adipocyte) it becomes obvious that food eating behavior is at least strongly related to, if not caused by, the fact the adipocyte is sequestering nutrition, stealing it from the blood, rendering it unavailable for energy use.

@TuckThe crappy Omega 6 in corn and soybean oal worsen glucose tolerance and can be expected to lead to higher insulin responses compared to items prepared with heavily monosaturated animal fats. I too observe problems eating omega 6 foods, such as acne and mood issues and lethargy but I am educated enough to know these are all downstream hyperinsulinemia, not some magical mythical IT BE THE FOOD REWARD. A nice monosaturated avocado will have me feeling quite fabulous.

Also, prepared bland disgusting starch foods is often loaded with designer MSG molecules that are insulinotropic agents. It would be like taking a unit of humalog or prandin before your meal. If you overdose your insulin responses, you are absolutely going to be hungrier shortly after eating. Same reason as these VMH lesioned rats: excessive insulin signalling will sequester nutrition from the blood excessively ~2hrs after eating, which will then drive up total energy consumption.

The problem is not the flavor, the problem is the things they add to foods to make them somewhat edible is a land mine for metabolic health. Again, it's not this magical FOOD REWARD but very real evidenced based documented mechanisms that crappy food flavor additives lead to weight gain and eating.

Losing minerals are a problem for any diet that works, not just low carb. The problem is caused by the favorable changes in insulin - insulin regulates electrolyte balance, and kidney processing of minerals, and when levels drop, electrolytes are wasted. Insulin STORES STUFF including minerals.

You also find these same issues with electrolyte wasting and the uncomfortable effects (sometimes fatal effects, if you have an arrhythmia) in other highly effective diet programs to drop insulin, such as doing PSMF or very low calorie intakes of high carb diet. What all of these interventions have in common is that they bring insulin down like cray cray.

I would mention that nuts are perfectly low carb and can be used in a ketogenic diet and are loaded in minerals. If you are warry of omega 6 I would also mention most nuts are high in monosaturated fat, not omega 6; they do contain some omega 6, but we DO NEED some omega 6.

I had observed my whole low carb life that nuts were the only food that made me feel "good", and I gravitated to eating them as a prmary energy source. My glucose tolerance seemed better, I did not get hypo as often, my appetite was lower, and my mood was better.

When I started taking magnesium citrate, I realized the benefit from nuts was the magnesium. It was one of my greatest findings to try and use the mag citrate.

I feel if you are glucose intolerant you SHOULD BE taking additional mag citrate anyway... refusing to supplement glucose tolerance enhancing nutrients because of some stupid paleo religious myth is like hindering yourself for no reason.

@BillThe interesting thing, is all of these animal models ultimately have the same mechanism: their hypothalamus is f*cked. The MSG and the toxic diet all destroy the rats hypothalamus, just like VMH lesioning. They really aren't different animal models , just different ways of causing the same/similar defect in the hypothalamus.

It's also interesting there are many genetic human disorders where there is damage to the hypothalamus, and these humans also become obese and cannot stop eating. For example, praeder willi syndrome involves this hypothalamic damage. Another key feature of praeder willi syndrome is hypogonadism. This is rather consistent with leptin deficiency so it is possible that obliterating the hypothalamus leptin sensitive neurons leads to a state as if one had no leptin at all - fat cell changes (stealing nutrition in the blood) and heightened eating behavior and energy-sparing infertility are the result.

http://ama-med.org.ar/obesidad/Prader_Lancet.pdf <--- these researchers put fourtht he hypothesis that the symptoms of a prader willi child is nothing more than a chronically activated adaptation to starvation secondary to hypothalamic malformation prenatally.

In praeder willi, it is found that ghrelin levels are abnormally elevated. This is highly suggestive of lack of normal leptin activity. As stated, leptin deficient humans also become very obese and food obsesed, and will have abnormally elevated ghrelin. It seems the brain damage from genetic abnormality is disrupting normal leptin signalling in the hypothalamus.

Ghrelin is controlled by insulin primarily, but another key regulator is LEPTIN. It is a signature of garden variety obesity that one has very low ghrelin after an overnight fast. This is because in obesity leptin signalling is in tact, but the problem is chronic unremitting hyperinsulinemia. Hyperinsulinemia leads to abnormally suppressed ghrelin upon waking. THe person wakes up from a fast, with an endocrine profile in the fed state! This is associated with being fat and growing fat. (Personally I have always noted that my appetite upon waking was highly predictive of body fat trends... waking up feeling as if I was fed has always been tightly associated with higher insulin and body fat gain, in my case).

@all:-"Start some ratties on D12492 and they will immediately double their calorie intake, on day 1."I highlighted the word immediately as it indicates that the ratties' appetites doubles before any damage has been done to anything.@john:-Even though intake of HFD was falling, intake of HFD was still > intake of chow. Hence, weight & fat mass was increasing. Dunno about set-points. To me, reward determines intake. For instance, where I'm concerned, chocolates are like class-A drugs. If I eat one, I really want to eat another immediately, then another. Did the first chocolate break my hypothalamus, make my fat cells super-sensitive to insulin, suck in too much glucose from my blood and make me want to eat another immediately? Insulin isn't that quick.Anyway, I don't want to get into an infinite loop arguing about stuff on the Internets.

The high fat diet was too palatable/rewarding, so they ate too much and got fat. But, their intake decreased soon after because it became boring (the reward value decreased). Of course, since they didn't lose fat after their diet became unrewarding, it's obvious that their setpoints were permanently heightened...

Peter,

The damaged pair-fed rats had heightened setpoints, so their bodies were lowering EE and conserving fat. The abnormal insulin secretion and signaling were simply side effects...

...is this seriously the kind of science and reasoning being used nowadays? As Woo mentioned, this is basically untestable/unfalsifiable. Food reward and setpoint theory should not even be recognized as a competitor to Peter's post so long as we have supportive evidence of abnormal insulin signaling right in our faces.

No. Liver, kidney, bone broth and egg yolks are pretty good sources of all nutrients. Leave the leaves for recreational purposes or to be eaten by Food.

George, the normal weight insulin resistant animal is a very interesting beast. I'll get to it sometime...

Its, I think the MRI studies will tell us something about chronic hypothalamic injury. The idea that they are limited to the VMH in obese folks is amusing. Just google gliosis in alzheimers or parkinsons.

Nigel, I seem to be missing something, food intake in kcals does rise for HFD before falling, it doubles... BTW, interesting as to how one might measure boredom in rats. A hyperpalatable, hyper rewarding food becomes a boring after 5 days. Those folks in the rat chow business need lessons from Kraft!

Also, how do you know the injury didn't happen on day 1???? No one looked until day 3...

Tuck, there's not a lot of linoleic acid in the butter oil study, the soybean oil was only 1g vs 19g butter oil.

David, Glutamate excitotoxicity is utterly non controversial. Getting exogenous glutamate to neurons outside of the neonatal period is more of a challenge. But these rats are MSG injured. It's a standard model.

Chocolate contains numerous psychoactive compounds. While chocolate also contains substrates for energy (fat, protein, carb), it also contains naturally occurring chemicals that mess with brain chemistry and promote changes in mood and behavior. Most drugs are of plant origin, such as heroin and cocaine, don't forget.

It would be like eating a brick of butter, laced with traces of marijuana, and then concluding that food reward mediates eating behavior. Obviously, if you eat butter with traces of THC, it's going to change how much you desire to eat that butter, because the psychoactive compounds in the food are screwing with your brain chemistry and dopamine.

Some people are genetically very sensitive to the psychoactive compounds in chocolate. I am not. I do enjoy chocolate and it seems to very slightly boost my mood, but I do not experience this drug-like response you seem to, and others do.

Similarly, I am extremely sensitive to caffeine (a compound in chocolate and other plant foods) meanwhile another person can drink a cup of coffee and experience no energy or elation. I am also very sensitive to green tea EGCG/catechins and they are more powerful than caffeine for me.

This is why food reward is retarded. Every person I have ever met who has ever provided evidence of food reward, is more easily explained by SCIENTIFICALLY REAL, documented, tested, evidenced based mechanisms.

People have gotten into this habit where any eating behavior which feels compulsive they attribute to "food reward", when in reality, their ignorance of metabolism and nutrition leads them to default to these explanations. It's not unlike some ignorant backwoods who points to clouds and rain and says 'it's raining, because god is making it rain". Um, no, science can explain very well why it is raining, and god is not real/untestible/unfalsifiable explanation, so thank you and have a nice day.

@Whoever: If something as enjoyable as sex can become less rewarding if it's with the same partner all the time, I'm fairly sure that the same effect can apply to food. See Coolidge effect.I'm not suggesting that insulin has nothing to do with obesity. I'm suggesting that it doesn't explain everything e.g. why some foods are more moreish than others.I'm also not suggesting that FR has everything to do with obesity.I'm suggesting that it explains some things.Anyway, bed time.

I would also at this point out, that deriving enjoyment from food and desiring repeat consumption, does not make one fat, and does not necessarily lead to obesity.

I observe thin people , weight gain resistant people, often have foods they like a lot because of flavor, and they will eat a lot of these foods when presented with them, but they still do not gain weight and over a long term trend of time, they adjust counterregulatory response for energy use and food intake patterns, and their body fat does not grow.

Only the endocrine system and metabolism can make your body fat grow, and it is pure wishful fantastical thinking to believe that food enjoyment mediates this process. Yes, I know, food enjoyment/palatability is not reward. As food reward has yet to be defined, and is merely retroactively defined by any over eating/fat growth phenomena, then it still remains that the food reward "hypothesis" is a joke.

The only reason it is even being investigated and studied by researchers is because obesity researchers operate from the biased, ignorant perspetive that obese people eat themselves to fatness and are flawed weak people with self control deficits.

Yep. What I said was "... you should indeed be cautious about minerals--especially potassium and magnesium, which tend to be depeleted by rapid weight loss..."

This is not just a caution about low-carb diets. It's a caution about minerals and rapid weight loss. Of course, very few diets other than low-carb diets actually produce prolonged rapid weight loss.

The Eades in their Protein Power scheme warn about depletion of magnesium and potassium, and most people are already low on both.

One has to be a little careful with potassium supplementation, and blood tests are wise.

On the other hand, magnesium basically monitors itself: Take too much, and your bowels will tell you to back off. But threre are limits on the rate of Mg absorption, and it can take a couple of years for a Mg-deficient person to get back to adequate levels. Blood tests don't work for Mg; the body keeps blood levels in a pretty tight range. If you are deficient, it will maintain this range by pulling Mg from tissues and bones.

Transdermal Mg is a pleasant way to approach the problem: Hot Epsom Salts baths, and/or "Magnesium Oil" (which isn't an oil at all, but a fully saturated MgCl solution. Easy to make on your own, and far cheaper than buying pre-made "oil." [Sure feels like an oil, though!])

Weight loss alone wasn't enough to bring down my blood pressure sufficiently. A year of Mg supplementation seems to have doen the trick.

@Nigel""Start some ratties on D12492 and they will immediately double their calorie intake, on day 1."I highlighted the word immediately as it indicates that the ratties' appetites doubles before any damage has been done to anything."

This is more than likely, nay, almost CERTAINLY, one of those things limited to "Rats only", and probably only a certain variety of prone rats bred for scientific experiments. There may exist a certain strain of rat, which is genetically predetermined to respond to a high fat intake, with a toxic respond and damage/death to the hypothalamus. Scientists select these rats, and then feed them fat, to study what happens in fat gain and obesity. If the rats are eating more on day 1, it may very well be that subclinical levels of damage are occuring as early as day 1. I can tell you as a former fat ass that if your insulin dynamics change in MINUTES you are eating more within MINUTES. If I eat a bowl of pasta right now, I can assure you within 2 hrs I will be trembly and shaky and sweaty and running to the fridge like a thriller zombie for FOODS. It's not unreasonable to assume that damage may occur as early as day 1 leading to changes in fat cell sensitivity and food intake.

Who knows. Either way, this mechanism has zero relationship to human obesity. I respond to a 60% fat diet with satiety and not being 280 pounds. I am a human being. My brain does not ASPLODE from butter and eggs. If I ate some kind of poison, maybe then my hypothalamus would ASPLODE, but I am more than genetically adapted to tolerate and thrive on ground beef fried in butter mixed with eggs and cheese (dinnaaaaar was gooooood so rewarding, apparently I can hardly button my size zero jeans oh noes! If I gain any more weight I will almost fit into a size medium!)

Even Stephan Guyenet stepped back from that craphill and REFUSED to extrapolate these findings to humans. Stephans own words re: d12492 and fat rats...

" We deliberately use rodent strains that are susceptible to obesity on this diet. Some strains are more resistant to obesity than others, but a comprehensive look at the literature reveals that high-fat diets are generally not good for rodents, and most strains tend to gain some amount of fat and develop long-term health problems on high-fat feed. There are a few exceptions in the literature if you look hard enough for them, but they are drowned out by the much greater number of studies showing harm.

So if we're deliberately selecting rodent strains that are particularly sensitive to fat gain on a purified high-fat diet, how can we generalize from this and say that dietary fat causes damage in the brain and obesity? The answer is that we can't, and we haven't. Nowhere in the paper does it say that dietary fat per se causes damage to the brain, or even causes obesity, and Drs. Thaler and Schwartz were careful not to say that in interviews either. We choose rodent strains that are susceptible to obesity on purified high-fat diets simply because we're studying obesity, and we know that feeding this diet to the right strains of rats and mice produces it readily. "

"....because obesity researchers operate from the biased, ignorant perspetive that obese people eat themselves to fatness and are flawed weak people with self control deficits."Seriously?I believe that the first part is true. People become over-fat by eating too much.The reasons why people are eating too much are many and varied and are listed in my blog, together with what can be done about it. Blaming people is not in the list.

You wrote that certain foods mess with brain chemistry which encourages repeated eating. What's wrong with using the term "Food Reward" to describe this effect? This effect involves brain chemistry rather than insulin, which is why it's immediate.

@Peter: I bet the rats' food kcals intake doubled after the first bite of D12492.

In regards the comments above about: the timing of damage after the rats started the high-fat diet (HFD)...

The Schwarz study discussed above states in its abstract... http://www.jci.org/articles/view/59660 "Here we report that unlike inflammation in peripheral tissues, which develops as a consequence of obesity, hypothalamic inflammatory signaling was evident in both rats and mice within 1 to 3 days of HFD onset, prior to substantial weight gain." ...my bold emphasis

And yet somehow, Schwarz, Guyenet et al seem to interpret this as obesity leading to hypothalamic damage... why not look at what the rats were eating instead?

@NigelBecause food reward is a nonsensical label that obsfucates the real scientific mechanisms certain food items may lead to obesity. It also assumes repeat consumption is synonymous with obesity when this is not the case. There are many thin chocolate addicts, and I have family members as thin as a stick who have certain food items they go crazy for...but they lack a genetic endocrine disorder to develop obesity, they lack energy using disorders, and so their body fat does not expand abnormally.

Also, the heightened eating is not always or even most of the time a reinforcement-reward process, there are many reasons it is occurring. Furthermore, falsely attributing this to a reinforcement/reward process by default for little rhyme or reason prevents a person from understanding and thus logically applying affective obesity management behaviors. For example, salt and pepper are not going to lead to obesity, even though they will make meals more palatable and enjoyable and increase desire for consumption. Adding fat to a meal will not lead to obesity if one manages their total carbohydrate content and tightly controls glucose and insulin responses, even if fat enhances palatability and desire for repeat consumption.

Chocolate is loaded with psychotropic agents. A person who compulsively eats chocolate is highly sensitive to the drugs in chocolate. Observing that chocolate leads to compulsive intake in some people, is like observing that ALCOHOL leads to compulsive drinking in other people. Alcohol also contains glucose and nutrition - why not call alcoholism food reward as well? Saying compulsive eating of chocolate is food reward is as stupid as saying compulsive drinking of alcohol is also food reward. No one with half a cortex would argue this because it's obvious the psychotropic agents of alcoholic beverages produce compulsive drinking in sensitive people - it's not the glucose/nutrition in alcohol, which are there by happenstance. The percentage of people who have control problems with chocolate drugs, are probably about the same of the percentage of people who have problems with alcohol or caffeine or any drug found in nature.

MSG directly induces insulin release greater than is required for the nutrition content of meal. Again, NOT a reward/reinforcement process, but a logical response to blood nutrition being not as available after eating, relative to a non-processed food meal, as a direct result of being loaded with MSG. The reward pathway is in tact, functioning normally, in response to an endocrine disturbance. If you take 1 mg of prandin while eating your box of pasta, or a can of broth and frozen vegetables, you are going to find yourself hungry and eating a lot ~2 hrs after your meal. It's not because the boyardee ravioli or the canned soup was so "rewarding", it's because the abnormal flavor agents literally lead your pancreas to overproduce insulin greater than required.

Calling all of these phenomena "food reward" Is scientifically and clinically WORTHLESS. Eating a bland diet will NOT help people to control obesity, particularly because bland diets which are high in starch are sub-optimal ways of controlling hyperinsulinemia compared to a diet with flavoring agents that is carbohyrate controlled. I assure you I am using body fat better after eating salt + pepper + sugar free ketchup eggs, than I would be eating a totally flavor neutral piece of bread, or white rice, or pasta. I am 29 years old and have been aware of glucose disorder since 20. I am absolutely CERTAIN this is the case. FLavor does not make you fat. Insulin signalling abnormalities make you fat, with fat cell hypersensitivity makes one fat.

There are endocrine disorders other than obesity, which feature disturbances of behavior that may superficially look like a reward-reinforcement disorder. Addiction.

http://en.wikipedia.org/wiki/Diabetes_insipidus

In diabetes insipidus, a person does not make ADH. This is a hormone that regulates fluid balance and sodium.

People with diabetes insipidus are driven to drink and drink and drink fluid. They never reach a point of satisfaction and quenched thirst, like a person without an ADH disorder. They exhibit dilute polyuria, and polydipsia, which gives rise to the name "diabetes insipidus" (as the 3 ps of diabetes are polyphagia polyuria and polydipsia, a person exhibiting diabetes insipidus is first suspected to have insulin deficiency i.e. diabetes mellitus type 1. Polyphagia is not a part of diabetes insipidus as energy metabolism is unaffected by ADH deficiency).

The person with ADH deficiency has a logical functional in tact reward pathway. THe reason water continues to be motivating and rewarding is because their endocrine system is not regulating physiology normally, leading to a non-terminating desire for fluid. This is a process mediated by reward pathways, but obviously, the problem is not a reward pathway disturbance, the problem is an endocrine disorder which is breaking physiology. Compulsive water drinking and urination are just symptoms.

This is why the "food reward" hypothesis of obesity is stupid, unscientific, and clinically worthless.

Food intake, over a long term period of time, is tightly regulated by our physiology, and it is a response to the nature of the adipose tissue. It is evolutionarily illogical to believe the fat tissue is passive victim of the brain. The only time this would be true is if the brain is damaged and cannot properly perceive fat-cell endocrine feedback e.g. praeder willi or any number of hypothalamic damaged rats.

The fat tissue is 1 on 1 in the battlefield to survive. The fat tissue TELLS THE BRAIN what to do, via endocrine signals such as leptin/energy availability from fat tissue. Hypothalamic damaged humans and rats are only so because they have blown up a critical spot for leptin receptors - they exhibit the physiological changes they do, because their body is operating as if they are starving to death even though their leptin levels are adequate enough. Hypothalamic damage leads to obesity specifically because it makes the brain unable to receive feedback from the fat tissue, and so the physiology defaults to a state of fat cell emaciation.

Anyone who does not have a damaged hypothalamus, who eats and grows extremely fat, almost certainly is exhibiting the effects of some sort of endocrine or metabolic disorder which impairs energy use from glucose leading to compensatory hyperinsulinemia and repartitioning of glucose as fat and stored in white adipocytes (at least, so long as they remain hypersensitive to fattening - or so long as insulin levels stay dramatically superphysiological - which ever is occurring and both may be).

Nigel said;-----------------------------------"Start some ratties on D12492 and they will immediately double their calorie intake, on day 1."I highlighted the word immediately as it indicates that the ratties' appetites doubles before any damage has been done to anything.-----------------------------------

Personally, I think all chow-fed from weaning animals are likely to have a bit of a metabolic learning disability.

I think I read about this in Norman Doidge's The Brain that Changes Itself. Rat pups, exposed to excessive white noise, develop a kind of epilepsy. Any time they hear anything at all, the whole audio cortex (or whatever you calls it) gets excited at once, and they have a fit. It's reversible, you can retrain the rats with simple tones so this doesn't happen.

I'd wager that when it does happen, there's some brain damage. So--interesting noises cause brain damage? Or, is it a trick, a set-up? The brain didn't learn to handle sound properly, so noise actually became dangerous to some of it's cells.

Now, you take an animal that ought to get its nutrition as a bit of this, a bit of that (self-selection). And, you wean it on a diet that totally wipes out some of what should have been its learned ability to control homeostasis--not just of fat, glucose and amino acids, but of every other nutrient you can think of. Teach it to expect this or that version of crap in a bag. Give it a food that's so bloody predictable, it knows it will get this much glucose, this much fat, this much salt from a given volume. Is this what it expects when it eats its usual chow--or when it eats any chow? If there's never been a difference, does it know when one shows up?

I wonder, does fat damage the hypothalamus, or merely "surprise" fat? In a way, when the hypothalamus is under attack, it's the nutritional cortex--the brain cells responsible for the sense of nutrition, that's being damaged.

That's interesting. Would it apply to rats that get set macro ratios but real food? Though many become obese on these "refined" diets, there are examples of "high fat" or "high meat" or "meat and milk" diets that do not make them fat, even with moderate sucrose.

What if the "surprise" was carbohydrates instead of fat?

As you suspect with ketogenic diets, they do switch mice from western (I think that's what they called it) to ketogenic in that 5% protein ketogenic study, and they lose the excess weight--so no fat surprise there.

After re-reading what you said above, I see what you mean about the continued weight gain. The fact that they're eating more than the control rats would be important if that [the intake of the controls] is their expenditure. But, with a decreasing food intake, the rate at least [of weight gain] should go down accordingly, which it doesn't.

Is the vertical axis on Graph F actual weight rather than weight gain as labelled? HFD rats are almost zero on day 1, but have double the intake compared to chow rats. If so, HFD rats get to over three times the weight of chow rats, suggesting a big drop in energy expenditure in HFD rats compared to chow rats.

I'm doing some research which is relevant to this thread. It will be complete in a few days.

"I would ban advertisements for manufactured foods & drinks. Advertisements encourage us to buy things that we don't need."

Yes, but this kind of thinking is very dangerous when someone else gets to decide what is good for us. It wouldn't be much of a leap for the government to decide to ban saturated fat and red meat for our own good and force us to eat a plant-based diet.

Gliosis and neuronal loss in certain brain regions are findings seen in various neurodegenerative disorders such as Alzheimer's disease, Korsakoff's syndrome, multiple system atrophy, prion disease, multiple sclerosis (after an acute attack) and AIDS dementia complex. It can also be found in Parkinson's disease, ALS and Huntington's disease.

It has also been associated with about 10% of patients with Celiac Disease or gluten-sensitivity (Archives of Neurology. 63(10):1440-6, 2006 Oct.). Gliosis damage to the brain in Celiac and gluten-sensitivity usually causes ataxia, peripheral neuropathy and/or cognitive impairment.

Because, Nigel, what you suggest is tantamount to lobbying for a nanny state government. You assume that people are too stupid to know what to put in their mouths and need the government to censor what they see and hear for their own good. It's not much of a leap for governments to start banning or highly taxing food groups, it's happening already. Look at the "fat tax" in Denmark.

If they just banned advertising for saturated fat and red meat without outright banning the foods, can you not see how that might affect availability eventually through lost revenues to the producers?

People need to think more carefully before they start screaming "there ought to be a law."

This comment is part of a thread that starts with my initial comment in ninth position from the top. Nobody remarks at all upon it until “Anon” replies in comment #31:

“Sorry, I’m afraid this town isn’t big enough for two utterly reliable sources on nutritional science.”

Despite the cloak of anonymity, I detect the unmistakable odor of the tapioca-encrusted fingers of Dr. Mark Harris having tapped out this reply. I mean, who else would care, except the congenitally thin-skinned neuroradiologist himself? Furthermore, the concise answer has all the earmarks of Dr. Harris’s pithy prose. So I clicked on the link. Not surprisingly, it connects to The Starchevore’s(sic) Recommended Blog List. At the top of this list is Whole Health Source. The following caption is underneath: “Dr. Stephan Guyenet is the utterly reliable source on nutritional science. What really did surprise me was that “Hyperlipid” had been deleted completely from the list.

I immediately loaded the Starchevore’s March 15, 2010 post: Insulin is Doorman at the Fat Cell Nightclub, Not a Lock on the Door. It is one of my many PaNu favorites. I quickly printed out a hard copy, as I fear it may also soon face revisionist deletion.

Take a long, hard look in the mirror, Dr. Hairless: You should be able to recognize the larval stage of Tim the Enchanter, 2.0! Of course, if its after dark, it’s more likely you’ll see the reflection of a sleek, hyperinsulinemic hairless mole rat, kicking back in the VIP Lounge of Stephan’s Rodent Cage Nightclub (having been granted access by the Food Reward Doorman himself).

Up the street, in the old Fat Cell Nightclub where we all used to party, the crystal clear sound system is cranking out the dub remix of The Beatles’ “GET BACK”:

It [Gliosis] has also been associated with about 10% of patients with Celiac Disease or gluten-sensitivity (Archives of Neurology. 63(10):1440-6, 2006 Oct.). Gliosis damage to the brain in Celiac and gluten-sensitivity usually causes ataxia, peripheral neuropathy and/or cognitive impairment.

"Are you saying that food manufacturers should be free to do whatever they want, without any regulation?"

The discussion was about free speech as it relates to advertising. The warning was to be careful about what we encourage our governments to do as they can and have taken more and more control over what we are allowed to do with our own bodies.

Wouldn't you agree that if pubs were forced to publicly state that their beer was salted and food manufacturers were forced to disclose every product ingredient (GMOs for instance) that people should be allowed to make their own purchasing decisions?

Some regulations are of course necessary but be careful about the ones for which you ask. Those that suppress free speech and freedom of information and therefore choice are typically abused by those with the most power.

For instance, in the US, Big Ag has been allowed to claim that oats are "heart healthy" but cherry and walnut growers are shut down for making any claims about the health benefits of their products.

"This is why food reward is retarded. Every person I have ever met who has ever provided evidence of food reward, is more easily explained by SCIENTIFICALLY REAL, documented, tested, evidenced based mechanisms."

This is also true of the hormesis theory of polyphenols. It too seems to be an unnecessary hypothesis that's unfalsifiable. This is actually the only point on which I disagree with Dr Harris, BTW. There may be hormetic effects, but it will be very hard to seperate them from the pharmacological (e.g. CYP450 effects) and the conditionally-essential (e.g. collagen-protecting).Besides, all of you plant sceptics drink coffee with your cream, don't you?

@George Henderson,the idea of supplemental antioxidants is based on a flawed 60 year old concept borrowed from the petroleum industry.

No exogenous antioxidants have never been shown to offer any tangible benefits in human RCts. In fact they are generally harmful.

Big Pharma has already largely abandoned research on polyphenols and other antioxidants because they simply don't work.

There are plenty of reasons to eat plant foods without invoking antioxidants. Plants have stimulant, sedative, antimicrobial, antihelminthic, anti-nausea, diuretic, anti-spasmodic and a host of other properties.

@ BLOGBLOG No exogenous antioxidants have never been shown to offer any tangible benefits in human RCtsBoth vitamin d and melatonin act as antioxidants. Natural production of these natural antioxidants declines with age.Replacing those missing antioxidants with exogenous supplies from supplements enables the more elderly readers here retain our cognitive function sufficiently to spot unsupportable claims.

Let's say you and me form a PAC or a super PAC or whatever, and collect lots of money from like-minded paleo types, and we start carpet-bombing the media with ads extolling the virtues of non-SAD food and demonizing SAD food and the neolithic agents of disease.

The legislature is shocked -- SHOCKED! -- and they pass a law banning such ads.

Body-builders who do resistance exercise shift nutrient partitioning away from fat mass towards muscle mass, leading to "muscular-slimness". If they eat at maintenance calories, they neither gain nor lose weight. This is known as "lean-bulking".

@ blogblog, "There are plenty of reasons to eat plant foods without invoking antioxidants. Plants have stimulant, sedative, antimicrobial, antihelminthic, anti-nausea, diuretic, anti-spasmodic and a host of other properties."Many of which are mediated by polyphenolic antioxidants, or by alkaloid antioxidants such as beta-carbolines, or even by carotenoids.I can even think of a context in which plant products may be conditionally essential - when offal is not available (it doesn't keep long in summer, when plants grow) in the paleo scheme, or off the menu for some reason in modern times. Offal supplies folic acid, vitamin A, extra minerals, choline.Leafy plants supply folic acid, vitamin A precursors, extra minerals, betaine (a choline substitute) and some choline.

Also, how useful would meat be if it did not supply carnitine, creatine, carnosine, retinol and hydroxycobalamin, antioxidants all?How important is the antoxidant action of ketone bodies on a low-carb, high fat diet?

@ Nigel, that doesn't refute Peter's theory; muscle cells burn energy, adipocytes store it. The flow-on effects on appetite could differ.As for Taubes, he writes about exercise being prescribed for weight-loss, not to healthy adults as in the study you cite.A healthy person can access all their energy stores, an obese person cannot, so the latter will feel hungrier after exercise.

@George Henderson: Peter wrote:-"As Taubes might comment, the rats then over-eat because they are losing calories in to their adipocytes."The study I cited shows that losing calories in to muscle cells doesn't cause over-eating.

You wrote:-"As for Taubes, he writes about exercise being prescribed for weight-loss, not to healthy adults as in the study you cite."What's that got do do with him writing that exercise works up an appetite? It doesn't.Exercise doesn't result in weight loss. The main purpose of exercise is to increase the insulin sensitivity of skeletal muscle.

You wrote:-"A healthy person can access all their energy stores, an obese person cannot, so the latter will feel hungrier after exercise."Can you provide evidence to support that statement? An obese person has higher serum FFA levels than a healthy person, so has better access to their energy stores than a healthy person.

Karl, gliosis is routine in neurodegenerative diseases. I've not looked at the brain areas in the study but if people on the route to T2 diabetes are not on the route to T3 diabetes (Alzheimers) I would be amazed. I guess you have to be a bit careful about which bits of the MRI you compare to the VMH to get the result you want. But I've not had time to look at the fine detail of where they looked in the human MRIs.

Nigel, Re graph F. As I see it the Chow column is total weight/fat gain in 14 days on chow. The columns 1d, 3d 7d etc are the total weight/fat gain in D12492 fed rats over the number of days specified. The comparable column to Chow is the one marked 14d on D12492. Thus you can compare weight/fat gains over 14 days. If you look at the amount of weight/fat gained on chow in 14d and add this to the amounts on 14d of D12492 you get roughly the amounts gained at 28d on D12492, exactly what you would expect if the calorie intakes where near identical for the last two weeks of the 28 days. I know it's an awful graph, ditto graph G. The authors probably have carb poisoning.

majkinetor, I think we have to be very leary of accepting anything this group posits. Autophagy can be good or bad depending on your circumstances.

Nigel, interesting study. Nice that caloric expenditure produces no drive to replenish the deficit. That should have the obesity epidemic sorted. I'm not quite convinced that the study tool (exercise) is quite the same as throwing a CNS switch controlling adipocyte insulin sensitivity.

You need to read a little about metabolic flexibility before suggesting that elevated FFAs in the obese mean that they have better access to energy supplies than the non obese.

Exercise won't sort the obesity epidemic because a "normal" amount of exercise makes an insignificant difference to body weight. Exercise is for increasing the insulin sensitivity of skeletal muscle. I consider exercise to be essential for IR people.

RE Metabolic flexibility: I read "Metabolic flexibility is the capacity for the organism to adapt fuel oxidation to fuel availability."An obese person has muscle glycogen, intramuscular triglycerides and higher serum FFAs. Therefore, whatever fuels muscles need for any intensity of exercise would appear to be readily available.

@ Nigel, exercise raises metabolism and temperature; so does digesting a meal. So there might be some switch that delays appetite after exercise to prevent overheating or overloading; under some conditions.If exercise gets the fat flowing from the adipocytes (and the rest of the body can use it efficiently) this might also be satisfying while it lasts.But this is of little use if these fine systems aren't working properly to start with.How long did that study last? 3 x 8-hour trials.Weightloss takes months, weight management is a lifelong project.Would these effects have persisted beyond the 8 hours, once metabolism returned to "normal" for these subjects?

As a nurse I have casually observed the majority of dementia patients have the following pre-existing vulnerabilities:

1) TYPE 2 diabetes2) VASCULAR disorders

To have a 87 year old looking for their mother and small child alone in a nursing home, to NOT also have a many year history of type 2 diabetes preceding, or some vascular disorder (e.g. a-fib or other vascular issue) is pretty rare.

It does happen sometimes you have dementias which exist in isolation of complex metabolic or vascular abnormalities, but those are probably genetic. Some people have genetic dementias, after all, where the brain dies in old age and there's nothing you can do about it.

The reason metabolic and vascular disorders lead to brain death in old age is precisely because these disorders rob the brain of energy nutrition.

Here is a scientific diagram explaining the process. Highly complicated.

No blood flow -> tissue metabolism asplodes! -> tissue death. If it happens in the heart, because of a clot, it's called a myocardial infarction (heart attack). If it happens as a sudden insult in the brain it's called a CVA (stroke) and it is associated with a sudden loss of ability, hemiparalysis, mood and personality and cognition changes. If it happens chronically, low grade, over a period of years, it's called vascular dementia. Vascular dementia is marked by long periods of stability followed by sudden sharp declines in cognition, which reflects the low grade vascular insults in the brain occurring to the person.

Metabolic disorders are different, cause dementia the same way they cause death of all other organs in your body - feet, and kidneys, and eyes. Slow decay. Evidence suggests the brain has insulin receptors, and brain IR is a risk factor for alzheimers and dementia.

Pretty common sight in the nursin' home: Demented, confused, blood sugar runs ~200 at any given time. Government rations of graham cracker snacks and frozen pasta meals and ignorant nutritionists planning these meals (eggs are bad way to spend our government / corporate nutritional allowances guys, they are high in saturated fat and raise cholesterol! MORE PASTA MEALS INSTEAD!)Physicians do not help, are just as stupid / apathetic, and pile on ineffective OGTs. For elderly patients in hospitals insulin therapy is considered temporary; no one educates the family / caregivers at home about the importance of taking your sugar at meals and covering your blood sugar. "At that age, I want to eat anything I want, anyway!" No one realizes the glucose metabolism disorder is the reason for all of these other diseases, including the heart breaking dimentia that leaves so many family members crying and frustrated mourning their still-living dead parents.

Those without hyperglycemia, have afib instead, and typically maintain semi decent cognition until they have enough insults that they end up babbling nonsense to no one, completely disoriented at all times. This sort of condition is less frustrating/ infuriating than the metabolic sort because it is less preventable, the person is more of a time bomb and the job of medicine is to delay or soften the next devastation to their brain. It's also true that IR and metabolic syndrome lead to the vascular disorders, so it's really not all that different in the end.

Anticoagulant therapies often do raise the risk for hemorrhagic CVAs. I've seen this happen more than once. Coumadin and plavix and asprin and uh oh, massive brain bleed all over the place. This can be very traumatic.

Oh and i would mention, vascular disorder + metabolic disorder = worse old age craziness then either alone, and these are the ones who are most apt to end up in nursing homes due to requiring 24/7 care/observation/protection from themselves.

I think exercise can help modulate hyperinsulinemia, just as carbohydrate restriction can, and total dietary energy restriction can.

The question is, how EFFECTIVE is this prescription, in real world, for a person who has been sick and diseased by metabolic disorder, presently weighs 300 pounds, barely has energy to lift their arms, is hungry all the time, has very low motivation from progressive central dopamine insensitivity, and so on?

Much like "food reward", the Colpo-like advice to "just exercise more" and "create a calorie deficit" and "increase insulin sensitivity" is IGNORANT of the reality of what it means to be obese and metabolically sick.

Asking a person in that shape to walk around the block a few times is like asking a normal fit person to run a marathon.

I know because I was there.

When you fix the energy abnormalities of obesity, food intake will decline, fat cell contents will empty, and gradually tolerance for activity, motivation, will increase all by THEMSELVES.

Forcing a fat person onto a treadmill is asking for physical injury, needless stress/distress, hypoglycemic attacks and discouragement. It would be like throwing a bird with a broken wing out the window. Cruel and unnecessary.

It is far more useful to attack the problem at the logical root: an inability to use energy normally; improving sensitivity to insulin and glucose oxidation via diet and nutrition and sleep patterns and a full endocrine work up.

NO ONE CHOOSES to sit around and not move. This is the sort of irrational religious-like moralizing that obesity is caused by "gluttony and sloth". This is why Stephan Guyenet and his mentors believe we are food addicts.

When you are truly naturally energetic and thin - and I have been there - sitting still is IMPOSSIBLE. No one makes that choice, it is made for you when your body is broken.

Try telling a fat person to eat less carbs by giving up foods from the list I wrote above and I bet that the vast majority will tell you to go f*ck yourself. They don't want to give up eating those foods. Why don't they want to give up eating those foods? Reward. To deny that reward has anything to do with excessive food consumption is as ludicrous as to deny that insulin has anything to do with it.I think that we're going to have to agree to disagree!

@George Hendersen,a vast number of compounds found in foods have antioxidant properties. This is a [coincidental] function of their chemical structure. However this doesn't mean that their metabolic role is to act as an antioxidant in either plants or animals

It has also been realised that a certain amount of oxidative stress is essential to health. In fact vigorous exercise works partly by causing temporary oxidative damage and inducing repair mechanisms.

Research into dietary antioxidants is now considered a dead end by researchers because they either offer no benefits or are harmful.

@George Hendersen,a vast number of compounds found in foods have antioxidant properties when chemically tested in laboratories. This is a [coincidental] function of their chemical structure. However this doesn't mean that their metabolic role is to act as an antioxidant in either plants or animals. In many cases supposed antioxidants actually increase oxidative damage in vitro.

It has also been realised that a certain amount of oxidative stress is essential to health. In fact vigorous exercise works partly by causing temporary oxidative damage and inducing repair mechanisms.

Research into dietary antioxidants is now considered a dead end by researchers because they either offer no benefits or are harmful.

It seems what actually happened is you had been on a low carb diet for a good long while, which then naturally progressed into walking more, due to being less metabolically sick / using body fat for energy.

Also, we are all starting from different points of unhealthiness, so it may be possible for one person to adopt some kind of exercise program right away - another person may have to improve their metabolic health (signified by losing weight) first before they feel it is even possible to expend extra energy in activities because they are so tired even basic tasks use up all resources. It's far more common to lose weight and then gradually begin moving or increase moving.

Perhaps your opinion is that most obese people would refuse to give up glucose foods, and it is because of reward, but in my case I would have gladly made the choice to stick to a LC diet if I had only known glucose was causing the problems. I would never have gotten as obese as I had.

I also do not think "reward" is the reason people refuse to do low carb diets, the most common reason I see is peer pressure and ridicule. Good thing I am immune to that. Bacon and eggs and sugar free ketchup and diet bread is a hell of a lot more rewarding than boiled potatoes and steamed meat.... and it is certainly more rewarding and enjoyable than vegetables without fats and lean meats and rice and pasta.

@ blogblog, In my initial poast I did not say that polyphenols worked as antioxidants; I said the effects were mainly pharmacological (e.g. CYP450 effects) or structural (OPCs and collagens) - not hormetic, which is a meaningless concept when related to such a complex and varied range of effects.So you attacked something I didn't write to begin with. There's not a lot of nutrition in a straw man.I should have been warned off by your reference to "the idea of supplemental antioxidants [being] based on a flawed 60 year old concept borrowed from the petroleum industry". This is as ad-hominen and irrelevant (and probably as untrue) as slagging off methadone on the grounds that it was named after Adolf Hitler.When pro-oxidants such as acetaminophen overwhelm endogenous antioxidant defenses, supplementary antioxidants (NAC, glutathione, alpha-lipoic acid) can and do save lives in hospital settings.In dogs, oral pre-treatment with the polyphenol blend silymarin boosted glutathione to similar protective levels (if this was due to hormesis, the much larger injections of sylibinin used as antiviral adjunct for HCV would be toxic, but this is not the case).That lipid-soluble antioxidants - tocopherols, tocotrienols, carotenoids, and xanthophylls - act as systemic antioxidants, reducing lipid peroxidation seems uncontroversial to me. This may be unimportant if PUFA is restricted - SFAs and other animal food components (which includes tocopherols, tocotrienols, xanthophylls, and carotenoids) may well be better antioxidants than plant products - as well as being more supportive of AO enzymes - but why restrict PUFAs, or aflatoxins, or benzylquinone, if you don't believe in free radicals and antioxidants?

But do bear in mind that what might be the main conduit of oxidative stress, superoxide radical, is a reducing radical, not an oxidising agent. Superoxide reduces NO. to produce peroxynitrite, transition metals to produce hydroxyl radical, and is metabolised by SOD to peroxide.So it is the oxidised form of ascorbic acid (dehydroascorbic acid) that stops superoxide and spares NO.. Some polyphenols that spare NO. might also work as oxidants (with systemic antioxidant effects) in this way; say, ginkgo or hawthorne.

This discussion about antioxidants is on consideration, perhaps more relevant to Pete's post than I originally supposed; the same damage to mitochondria that prevents proper OXPHOS also produces elevated superoxide. Aubrey de Grey's hypothesis http://www.sens.org/files/pdf/mmmmmm.pdf has a good description of the role of mitochondrial mutation in generating superoxide.What you find in diseases featuring oxidative stress - e.g. hepatitis or pancreatitis - is that increasing antioxidant intake globally tends to improve them, whereas just using one over-hyped supplement will give very spotty results. It's a whole system in failure, not a deficiency of one unusual thing.Note that de Grey has reductive stress (high HADH:NAD ratio) as primary driver of OS. Posited by Ghyczy and Boros (below) to relieve RS are electrophilic methyl groups; choline, betaine, SAMe, carnitine, and the fishy-smelling stuff from fish ... trimethyl-N-oxide? Mostly from animal foods, in any case.journals.cambridge.org/abstract_S0007114501000642"Reductive stress, characterised by an increased NADH:NAD+ ratio,may be as common and as important a consequence of redoximbalance as oxidative stress.It may also be an important predisposing cause of the generation of reactive oxygen species.Considerable experimental and indirect clinical evidencesuggests that protection against reductive stress depends onbiomolecules with electrophilic methyl groups (EMG) such as S-adenosylmethionine, betaine, carnitine and phosphatidylcholine.Pathological processes leading to reductive stress and their reliefby such protective agents is reviewed and the proposed molecularmechanism is outlined.These and other EMG-containing biomolecules are part of the dailydiet and may represent an important control system for redox balance."

-2 ounces fried ground beef-half an ounce of cheddar cheese-1 avocado with tomatoes and green onions and lemon juice and sea salt-Tortilla chips with salsa (the chips are made of flax + corn from trader joes and have 9 grams of carb/glucose per serving)-a few fresh strawberries

Please explain to me how a "normal" calorie restricted diet allows for this sort of awesomeness of flavor? If I was trying to CICO while maintaining a high % of dietary carb I would have to cut out all the delicious fatty foods and replace them with disgusting tasteless low fat alternatives... and my calories would also be supplied by disgusting tasteless starches from breads, potatoes, and rice.

Not only would I be hypoglycemic and fatigued and feel relatively horrible if I did this, by forcing my body to use glucose for fuel when it does not use glucose very well...but my diet would be by far less appealing from an emotional perspective.

Starch is peasant food. It is cheap. It is intended to provide calories to a lot of people for not a lot of investment. When human beings invented agriculture, we invented the sprawling hive-like modern agricultural society. This is a function of gross quantities of cheap calories which were unheard of prior to the invention of agriculture. Whereas hunter-gatherer bands can only support a few dozen people before they max out on nutrition/calories, agricultural societies can support thousands and thousands of people by malnourishing them with cheap mass produced nutrient-depleted glucose. Traditional agricultural societies are not that much different than 2012 western society in terms of nutritional quality of food - they also had endemic nutritional deficiencies and stunted growth and such things as a result of eating a really depleted and unhealthy grain based diet.

The only difference is in 2012 via factory farming of animals we can create cheap protein and fat calories for the peasants, as well as refined glucose, in addition to cheap glucose (starches) so now we also have macrosomia + obesity in addition to the usual deficiences always problematic since agriculture began.

One thing you can't say about low carb is that it is BORING and that a "normal diet" is more rewarding.

Sure, a totally unrestricted diet allows for maximum flavor/enjoyment of food... but then again, a totally unrestricted diet is not known for its ability to inhibit obesity. Only low fat/calorie diets and low carbohydrate diets have this power, as these diets both control abnormal hyperinsulinemia.

I would rather control hyperinsulinemia effortlessly by opting out of glucose food, rather than starving myself most of the day and white knuckling through post prandial sugar drops.

It seems what actually happened is you had been on a low carb diet for a good long while, which then naturally progressed into walking more, due to being less metabolically sick / using body fat for energy."

Whether or not you believe me makes no difference to me, but may affect you. If people tell you facts about themselves which don't fit your theory and you reply "That's irrelevant/you're mistaken/you're lying", they will think you're a nut-case.

My life history is in my blog. You can read the reasons why I chose to be sedentary and why I chose to move more.

I've asked people why they eat what they eat. The reply given is that they enjoy it i.e. it's rewarding. How many people have you asked and what replies did you get?

What works for you may not work for the general population, as you are leptin-deficient IIRC.

You said, "I've asked people why they eat what they eat. The reply given is that they enjoy it i.e. it's rewarding."

C'mon now, if you don't see the error(s) in using a statement like this to make your point then you don't deserve credibility or attention.

When Stephan first referenced the Ensure study, which was before he started pushing "food reward," I thought, "This is an interesting study. I wonder if he is going to come back to it in the future" (I didn't care quite enough to look into it on my own).

Unfortunately, after about a year (or whatever it's been) of continually reading posts and references, I've settled on the fact that this idea [food reward] is nothing more than an unscientific wild-goose chase. Pretty much I've learned that certain foods taste better and can cause cravings...but wait, I already learned that when I was a toddler.

If you asked me when I was 280 pounds why I ate a full sized serving of chinese food, egg roll, duck sauce, and several glasses of "iced tea", I would tell you that the food tasted good.

IF you asked me when I was 104 pounds after having lost from 280 why I always wanted to eat endlessly and never stop, I might have told you it's because food is really good. I actually began to believe in the hypothesis of food addiction for a brief , transient period back in those days. I've been where you are already.Why I did things like restrict calories heavily one day so I could go to buffets and eat an unlimited amount the next... or cook and look at recipies and watch the food network ALL THE TIME... oh yes, I absolutely was obsessed with food. This is not a foreign concept to me.

Talk to me today after having resolved the bulk of the physical disorders leading to food preoccupation, and I would tell you that:1) I barely care about my next meal2) Food is no longer that important3) I do enjoy food when eating it, but I stop thinking about it otherwise

Today I do none of these things; I do not cook, read recipes, watch the food network, and it's because when your body is healthy and works right food just isn't that important.

This is because today my metabolism is more normal than it ever has been, and I am as close to a naturally thin person as I ever have been.The only time my interest in food was more apathetic was when I was taking replacement doses of leptin. Unfortunately this is not a FDA approved treatment for morbid obesity yet, and never will be if Guyenet is the future of obesity research and various ignoramouses on the internet encourage his myopic, uninsightful perspectives.

I find it easy to believe fat people think they are food addicts. I've talked to many of them.I pity them all, because I've been where they have all been, and I know the real reason a person is forever preoccupied wth eating is cell-level energy using defects and endocrine abnormalites which are being fed back to the brain leading to a constant: EAT GOD DAMN IT.

Trust me nigel, there really does exist a space where people eat a meal and they just don't care about food otherwise. In that space, you don't fall off your low carb diet, because you aren't obsessed with eating.

Why can people with celiac disease relatively easily stick to a low wheat diet, and there isn't any accusations that they are "wheat addicts" and they shouldn't bother with it?

Saying that obese people should avoid insulin control (carb restriction) because they are addicted to food instead sort of doesn't make sense. Addiction does not make your body fat grow pathologically. As Peter has definitively shown in the FIRKO mouse, adipocyte insulin signalling makes your fat tissue grow, regardless of what the brain is doing.Restricting carbohydrate is a very effective method for ameliorating hyperinsulinemia . Not in all people, but MOST obese people.

It is more common to have done very well on low carb, and to stop when your family friends and doctors berate you so often that you are tried of feeling like an outcast, that you begin eating "Normally" which more often than not results in a return of abnormal hunger and fat growth.

Well yes I too wish I could eat anything and not be fat, but this is not realistic.

I was responding to your belief that low carb diets are less realistic prescriptions than are exercise programs for obese people.

I disagree entirely for the reasons outlined above. Exercise is something that is adopted LATER DOWN THE ROAD, after the metabolism and glucose tolerance/use has improved a bit via insulin correcting / body fat oxidizing dietary changes... when the metabolic state has improved enough that one can conceive of using energy wastefully in activities such as exercising.

Also, for this reason, exercise is at best a supplemental intervention, clearly subordinate to the importance of maintaining an insulin-controlling dietary program (usually restricted of carbohydrate as well as total caloric nutrition).

Exercise, IMO, is like magnesium citrate, or carnitine, or EGCG - it just helps the overall picture, but the #1 important modification is going to always be diet.

You can do a strict very low cal, or you can do a slightly low cal but strict low carb, or you can fast all day and have 1 meal per day...or somecombination of these... there are many dietary approaches that can control a tendency to hyperinsulinemia and inhibited body fat oxidation.

I'll tell you waht DOES NOT help obesity. Avoiding flavorful food and "reward".

This is like using exorcisms to treat schizophrenia. Nonsense. Religious myth. The few times it does work, the mechanism of action is clearly mediated by changes in insulin signalling in fat tissue secondary to reduced calorie intake... and most likely this will be temporary once the person adapts to the reduction of flavor/lower sensation diet, they will increase their eating again and regain the body fat, UNLESS they specifically maintain the hypoinsulinemic condition by not eating lots of calories and/or lots of carbs.

When one examines all the dietary options for achieving insulin reductions... long term speaking it is much more psychologically healthy and sustainable to just opt out of glucose food. You can only deal with hunger at night before bed for so long before you say "fuck it" and just eat a lot of pizza the next day.

Oh and I am of the firm opinion that the reason most obese people find it SO HARD to "give up the food they love" is because they have ZERO SUPPORT from the medical community.

If a fat person asks an authority: doctor, nutritionist, fitness freak... if they ask them "how should I lose weight" all of them will chime in unison EAT LESS CALORIES.

If the fat person asks: "Is it necessary , or helpful, to give up carbohydrates or reduce them?" all of these will respond in unison THAT IS UNSCIENTIFIC MYTH AND NONSENSE ONLY CALORIES MATTER.

If a fat person looks at government advice on what to eat, he is informed 60% of his diet should comprise of peasant starch food for idea health.

IN this sort of world, unless you are possessed of an unusually independent-minded CNS, slightly autie, or some other variant of socially atypical, odds are better than not you will decide that giving up english muffins for breakfast is not something you are willing to do.

Now, if fat people lived in a world where Guyenet-like thinking did not prevail, I think we would see many, many more fat people making the choice to adopt a low carbohydrate strategy to insulin management.

The only difficulty is emotional, related to social ostracism... and if one does not have sufficient confidence of mind/isolation from others to completely ignore the global ignorance surrounding them, and instead LISTEN to their BODY which works so much more normally off glucose (normal hunger, normal fat use patterns)... well then yes you too might decided that you are UNWILLING to give up socially acceptable diets.

I think the main difference between myself, and others who cannot stick to low carb, is primarily a social one. I don't give a shit what anyone thinks or says and I am rather confident in my ability to analyze and understand. I don't think experts necessarily know more than me or have more insight than I do. I have never clamored to gurus or worshiped at anyone's altar. I also do not care at all when people stare at me funny, and point it out, if I am eating the cheese part and not the bread part of a pizza.

From what I can see, most people tend to gravitate to gurus and experts to do their thinking for them, and find it impossible to fully believe in their own intuition and experiences. Most people will eventually cave in after enough time of being told they are freaks for eating strangely.

There is zero support for low carbing in the real world. ZERO.

This is a major influence over why fat people "decide" living without carbs is too much of a sacrifice, and a pointless one.

Food intake and body composition in novice athletes during a training period to run a marathon.Janssen GM, Graef CJ, Saris WH.SourceDepartment of Human Biology, University of Limburg, Maastricht, The Netherlands.AbstractThe change in diet and body composition was studied in a group of 9 female and 18 male subjects, starting a training program for 18 months with the ultimate goal of running the marathon. Mean daily intakes from 7-day dietary records for macro- and micronutrients were calculated at the start, after 1 year of training, and just before running the marathon. Anthropometric measurements were taken on the same occasions. In males the body fat mass decreased 2.4 kg, while in females no change in body composition was observed over the 18-month training period. Energy intake increased significantly in males from 131 to 159 kJ/kg/day. In women no significant change was recorded (141 to 147 kJ/kg/day). However, in both sexes CHO intake was significantly higher after 18 months (males 63.7-81.7 kJ/kg, females 68.0-81.9 kJ/kg). Also En% CHO increased significantly in males from 48 to 52 EN% and in females from 47 to 55 En%. This extra energy intake of CHO in women was covered at the expense of dietary fat. These changes in food habits in both groups are favorable in relation to the nutritional guidelines for better cardiovascular health. Whether the sex difference found in economizing energy exchange as a response to an intensive training program is based on an increased food efficiency will require further investigation.

http://www.ncbi.nlm.nih.gov/pubmed/2744924

In these free-living humans, training for, and ultimately running, a marathon over a period of 18 months resulted in a decrease in fat-mass of a little over 5 lbs. for men and no decrease in fat-mass for women. This suggests that an increase in caloric expenditure alone has very little effect on fat-mass in men, and no effect on women.

Also, while the abstract doesn't discuss activity levels outside of training, the men, but not the women, increased caloric intake by about 20%. This suggests that, at least in men, prolonged vigorous exercise has the effect of increasing appetite in the long-term.

If we assume that five pounds of fat contain roughly 17,500 calories (5 x 3500) then 18 months of marathon training "suppressed" appetite to the tune of 32 calories/day.

"The change in diet and body composition was studied in a group of 9 female and 18 male subjects, starting a training program for 18 months with the ultimate goal of running the marathon."The goal wasn't to lose weight or fat mass."Energy intake increased significantly in males from 131 to 159 kJ/kg/day."Was this due to increased appetite or because the men were told to carb load as part of the training instructions? We don't know.All we do know is that it sucks to be female! ;-p

Peter, I have been following these musings and arguments and discussions now for the better part of three to four years, Ever since in fact since I began to have health issues that according to the SACD I should not have. With my beloved a graduate from the Wageningen Nutrition Studies Department. I am a little bit disappointed that most of these 'studies' seem to me all dealing with issues that in my honest opinion are just one or two bridges too far. They all seem to be in essence observational studies, and to me it does not make a structural difference whether the observation takes place in a controlled environment or not. There simply are too many confounders at this level to be properly accounted for. At best we can arrive at a hypothesis with strong or less strong indications of a possible link and maybe even causal. The only thing and absolutely only thing that we can determine that two or several events are happening concurrently. This fact was driven home a bit more when I went through the work that was( and is being done at Liege university in Belgium, the work by Bruce Spiegelman, Stephen Farmer and others. Jack Kruse is beginning to make more sense every day .http://jackkruse.com/the-quilthow-to-beat-agin/#ROSI am not arguing that certain things don't work because they doFeinman, Volek, and Westman seem to make it work. http://rdfeinman.wordpress.com/2012/03/26/dietary-carbohydrate-restriction-in-the-management-of-diabetes-the-15-theses/I don't know what Stephan is up to this time or whether he will come with a mea culpa down the road again.

I appreciate your posts. Your statement 'NO ONE CHOOSES to sit around and not move. This is the sort of irrational religious-like moralizing that obesity is caused by "gluttony and sloth".' resonates strongly with me.

In the CFS community, there are medical opinion leaders who believe "Patients are not actually sick. They choose to lie in bed 23 hours a day, with no function, no social life and no joy - all so they can collect below poverty level disability benefits." I mean what the f*&k? How can a sane person think that anyone would live like that voluntarily???

I wonder about your arguments concerning obesity and why people won't give up carbs. I am not obese (50 years old, < 12% bf) but I have serious energy issues. So 15 months ago, I decided to give up wheat, sugar and vegetable oils. The wheat avoidance has been trivial, and I am happy to avoid the vegetable oils(although very difficult when eating out). So it's not will power. But the sugar avoidance has been very, very, very difficult. I crave sugar all the time. Within seconds of it touching my mouth, my brain lights up. It feels fantastic to eat it. I smiled at your 1.5 oz of nuts as an example of enjoying enjoying food. I could easily eat 1 kg of chocolate covered almonds at a sitting - many days in a row. And the reaction is instantaneous - pure joy.

One of my parents is obese and has type 2 diabetes. When I suggest to them that they could lose weight and ease their metabolic problems by going low carb, their response is: 'what? you mean I can't have my toast, and my cookies and my juice and my...?' The thought of going without those things is much worse to them than the current state of their health. I think this is what Nigel is talking about.

I don't know what all this means, and I intuitively dislike the term 'food reward', but I can't help thinking there is a central brain process involved here.

I do fully agree with you that if I could convince someone to change their diet for health, it would be waaaaay easier to go tasty low-carb than to try to go bland. Who in our society would ever want to intentionally eat bland non-tasty foods all the time?

Here's a wild-goose-chase candidate for buggering up human VFH: acrylamide.The stuff is neurotoxic, which helps, and it's highly associated with the usual obesigenic suspect foods; french fries, bread, donuts etc, (especially when fried in fat containing silicon antifoaming agents, apparently).Anything starchy or sweet and cooked at high temperatures.

http://care.diabetesjournals.org/content/32/12/2206.abstract

Association Among Acrylamide, Blood Insulin, and Insulin Resistance in Adults

it is also found in coffee, prune juice, and cigarette smoke.This is a relatively new discovery, most research seems to be on Science direct:

http://www.sciencedirect.com/science/article/pii/S0161813X0700160X

Acrylamide (ACR) is a neurotoxicant known to produce peripheral neuropathy in rats and humans, but little is known of its potential for producing cognitive or motivational alterations. Chronic exposure to low doses of ACR as a food contaminant is known to occur widely in humans. This research evaluated the effects of daily ACR exposure on food-motivated behavior, with exposures beginning prenatally on gestation day 6 and continuing through approximately postnatal day (PND) 85. Plug-positive Fischer 344 dams (9–10 per dose) were gavaged daily with 0, 0.1, 0.3, 1.0 or 5.0 mg/kg/day ACR. On PNDs 1–22, pups were gavaged with the same dose their dam had received. On PND 22, pups were weaned and pair-housed with a same-sex littermate and ACR exposure continued at 0, 1, 3, 10 and 50 ppm via drinking water. One male and one female pup per litter were tested in an operant chamber under a progressive ratio (PR) schedule of food reinforcement from approximately 6 to 12 weeks of age. Results over 6 weeks of testing indicated a significant treatment effect of ACR on number of reinforcers earned, with Tukey HSD post hoc tests revealing significantly fewer reinforcers earned in the 5.0 mg/kg/day dose group than in controls. A significant effect of ACR on response rate was also observed, with the Tukey HSD post hoc tests revealing a significantly lower response rate in the 5.0 mg/kg/day group than in controls. No effects of ACR were observed on post-reinforcement pause. These data suggest that daily ACR exposure at 5.0 mg/kg/day can produce measurable decrements on aspects of food-motivated behavior.

About Me

I am Petro Dobromylskyj, always known as Peter. I'm a vet, trained at the RVC, London University. I was fortunate enough to intercalate a BSc degree in physiology in to my veterinary degree. I was even more fortunate to study under Patrick Wall at UCH, who set me on course to become a veterinary anaesthetist, mostly working on acute pain control. That led to the Certificate then Diploma in Veterinary Anaesthesia and enough publications to allow me to enter the European College of Veterinary Anaesthesia and Analgesia as a de facto founding member. Anaesthesia teaches you a lot. Basic science is combined with the occasional need to act rapidly. Wrong decisions can reward you with catastrophe in seconds. Thinking is mandatory.
I stumbled on to nutrition completely by accident. Once you have been taught to think, it's hard to stop. I think about lots of things. These are some of them.

Organisation (or lack of it)!

The "labels" function on this blog has been used to function as an index and I've tended to group similar subjects together by using labels starting with identical text. If they're numbered within a similar label, start with (1). The archive is predominantly to show the posts I've put up in the last month, if people want to keep track of recent goings on. I might change it to the previous week if I ever get to time to put up enough posts in a week to justify it. That seems to be the best I can do within the limits of this blogging software!